Detection of MUM1/IRF4-IgH fusion in multiple myeloma

MUM1 (multiple myeloma oncogene 1)/IRF4 (interferon regulatory factor 4) ge ne has been identified as an oncogene transcriptionally activated by t(6;14 )(p25;q32) chromosomal translocation in multiple myeloma (MFA). The signifi cance of this alteration in MM remains unknown, as it is not detectable by means of conventional cytogenetic analysis. To address this issue, we estab lished diagnostic procedures based on pulsed-field gel electrophoresis (PFG E) analysis and double color fluorescence in site hybridization (DCFISH) us ing DNA probes derived from the MUM1 and the immunoglobulin heavy chain (Ig H) gene loci. Among a panel of 17 MM cell lines, three (17.6%) showed fusio ns between these two loci, which resulted in the juxtaposition of the MUM1 to the IgH 3' alpha-enhancer region by virtue of t(6;14) or insertion of th e IgH sequences into the vicinity of the MUM1 gene and in the concomitant o verexpression of the MUM1 mRNA. With similar results, fusions between MUM1 and IgH loci were observed by means of interphase DCFISH in eight (21.1%) o ut of the 38 MM cases, although no definite relationships between MUM1 stat us and specific clinical findings could be established.